Understanding the consequences of pesticide exposure is a focal point pollination ecology and global change research. Neonicotinoid pesticides are commonly found in floral nectar, where they can have well-documented negative effects on bee health and foraging behavior. Additionally, floral nectar often contains secondary metabolites that can positively or negatively affect pollinator physiology and behavior. We examine the combined effects of consuming nectar secondary metabolites and neonicotinoid pesticides on the bumble bee species Bombus impatiens, asking how a diet containing secondary metabolites mediates bees’ responses to an acute dose of a pesticide. In a laboratory experiment (n = 960 bees), we quantify worker longevity, activity level, and immune system performance under different diet and pesticide exposure regimes. We test three well-studied secondary metabolite compounds: caffeine, thymol, and digoxin in combination with an ecologically-realistic dose of imidacloprid, a neonicotinoid. We found compound-specific effects in all three responses. Combined consumption of imidacloprid and thymol reduced longevity in workers compared to a control and of either chemical alone. Caffeine extended longevity when bees did not consume a pesticide, but the benefit was lost when caffeine and imidacloprid were consumed in combination. Pesticide-exposed workers were less active than non-exposed workers 24 hours post-exposure, however most bees regained activity 72 hours post-exposure, with the exception of bees that consumed digoxin. Counterintuitively, an acute dose of imidacloprid increased phenoloxidase expression. Overall, we report how nectar secondary metabolites can complicate our understanding of the effects of pesticides on pollinator populations.